Journal of Toxicology & Environmental Health Part A: Current Issues

Susanne Becker, Joleen M. Soukup,

doi: 10.1080/009841099157539pmid: 10494914

Epidemiology studies associate increased pulmonary morbidity with episodes of high particulate air pollution (size range 0.1-10 mum diameter, PM10). Pneumonia, often viral in origin, is increased following episodes of high PM10 pollution. Therefore, this study was undertaken to investigate how PM10 alters airway inflammatory responses to respiratory syncytial virus (RSV), a frequent cause of viral pneumonia in infants and the elderly. Supernatants of unexposed and PM10-exposed alveolar macrophage (AM) cultured with uninfected or RSV-infected airway epithelial cells were assessed for a number of chemokines responsible for inflammatory responses in the lung. AM exposure to PM10 in the absence of infection resulted in a significant increase in interleukin (IL)-8 and macrophage inflammatory protein (MIP)-1 apha production but not in MIP-1 beta or monocyte chemotactic protein (MCP)-1. AM responded to RSV infection by the production of IL-8, MIP-1 alpha, MIP-1 beta, and MCP-1, while RANTES was derived solely from the RSV-infected bronchial epithelial cell line BEAS-2B. In the presence of PM10, the AM response to RSV was blunted. RSV-induced MCP-1 was significantly decreased, and the levels of MIP-1 and IL-8 were lower than expected from a combined response to PM10 and RSV. Furthermore, AM analyzed for uptake of virus showed a 50% decrease in viral antigen when exposed to PM10. RSV-induced production of RANTES by epithelial cells was decreased in the presence of AM but not affected by PM10 exposure. Taken together, these results suggest that AM-regulated inflammatory responses to viral infection are altered by exposure to PM10 in a manner that may result in increased spread of infection and thus may increase viral pneumonia-related hospital admissions.

Mi-Gyung Lee, Shiguang Li, Bruce B. Jarvis, James J. Pestka,

doi: 10.1080/009841099157548pmid: 10494915

The macrocyclic trichothecenes are a group of potent protein synthesis inhibitors that have been encountered in indoor air and food as a result of infestation by the fungus Stachybotrys. To evaluate the capacity of these mycotoxins to alter immune functions, the effects of satratoxin G, H, F, roridin A, and verrucarin A on interleukin 2 (IL-2) production and viability were evaluated in a murine T-cell model. EL-4 thymoma cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin and concurrently exposed to various concentrations of the trichothecenes. Enzyme-linked immunosorbent assay (ELISA) of supernatants revealed that IL-2 concentrations at 24 and 72 h were significantly increased in cultures that were incubated in the presence of 0.5 to 1 ng/ml of satratoxin H, 1 to 5 ng/ml of isosatratoxin F, 0.1 to 0.5 ng/ml of roridin A, and 0.25 to 0.5 ng/ml of verrucarin A. However, IL-2 levels at these time points were significantly depressed when incubated in the presence of higher concentrations of satratoxin G ( 2.5 ng/ml), satratoxin H and isosatratoxin F ( 5 ng/ml), and roridin A and verrucarin A ( 1 ng/ ml). Cell viability, as measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, was depressed by each of the trichothecenes in a concentration-dependent manner. MTT responses were significantly decreased by as little as 0.5 ng/ml satratoxin G, roridin A, and verrucarin A and by 2.5 ng/ml of isosatratoxin F and satratoxin H. When these data were compared to those found in EL-4 cells for the 8-ketotrichothecene vomitoxin ( deoxynivalenol) , a common food contaminant, the macrocyclic trichothecenes were at least 100 times more potent. The results indicate that, at low concentrations, macrocyclic trichothecenes as a group could superinduce IL-2 production even while partially decreasing cell viability, whereas higher concentrations suppressed cytokine production and were markedly cytotoxic. The capacity of these compounds to dysregulate cytokine production in a biphasic fashion may play an etiologic role in outbreaks of human illnesses associated with indoor Stachybotrys contamination.

L. Ganesh, J. M. Scarlett, D. J. Lisk, B. S. Shane,

doi: 10.1080/009841099157557pmid: 10494916

Epidemiological studies suggest a higher risk of hematopoietic disorders including lymphoma among cosmetologists. The etiology of these disorders among cosmetologists is unknown, but beauticians are exposed to a wide variety of chemicals in the workplace. In this study, the urinary mutagenicity of cosmetologists was studied as an indicator of occupational exposure. A microsuspension modification of the Ames assay with Salmonella typhimurium strain TA98 was used to detect direct-acting mutagens and promutagens in urine. A comparable group of teachers of similar age and gender, and living in the same geographic area was used as the control group. There was no elevated risk for urinary mutagenicity among the cosmetologists after controlling for a number of confounders including smoking. In a multivariate model, smoking regularly or within 24 h of sample collection was found to be positively associated with urinary mutagenicity among both groups. The number of cigarettes smoked daily, age, and length of employment were not associated with urinary mutagenicity. Analysis of urine samples collected successively from each participant showed a fair to good agreement between promutagens in samples, suggesting a fairly constant exposure to promutagens.

Kevin K. Divine, Felix Ayala-Fierro, David S. Barber, Dean E. Carter,

doi: 10.1080/009841099157566pmid: 10494917

Speciation plays a profound if not dominant role in both transport and toxicity of Hg(II). Hg(II) has a high affinity for sulfhydryl groups. The formation constant for Hg2+ and the anionic form of a sulfhydryl group R-S- is 1010 higher than that for the carboxyl or amino groups. The kidneys are the target organ for Hg(II) toxicity and the primary site of Hg(II) accumulation. Sulfhydryl groups have been implicated in both transport and nephrotoxicity; however, the role endogenous thiol compounds play in these parameters is not clear. The roles that albumin, glutathione, and the glutathione-derived complexes cysteinylglycine and L-cysteine play in toxicity and accumulation of HgCl2 were studied in LLC-PK1 cells incubated with different Hg(II):thiol ratios. In cysteine-containing medium, almost all 1:2 Hg(II):thiol complexes protected against Hg(II) toxicity up to 120 muM Hg, increased membrane-bound Hg(II), and decreased intracellular Hg(II) accumulation. In cysteine-free medium, all 1:1 Hg(II):thiol complexes were as toxic as uncomplexed Hg(II), and almost all 1:2 Hg(II):thiol complexes protected at 20 muM Hg, except albumin, which protected at 20 muM Hg. In cysteine-free but cystine-containing medium, two 1:1 Hg(II):thiol complexes were toxic at 80 muM Hg and two provided complete protection. All 1:2 complexes provided protection at 80-160 muM Hg. This investigation used defined media to demonstrate that mercury cytotoxicity in LLC-PK1 cells was dependent on Hg(II) concentration, the ligand, and the presence of a cysteine source for the cells. These effects were only partially explained by intracellular Hg(II) levels.

Rui Wang, Xin-Tao Wang, Lingyun Wu, Mircea-Alexandru Mateescu,

doi: 10.1080/009841099157575pmid: 10494918

The adverse effects of heavy metal ions on the heart functions of lower vertebrates are largely unknown. In the present study, the effects of Cd2+, Cu2+, and Cu+ on the cardiac functions of the heart isolated from dogfish shark, Squalus acanthias, including the epicardial electrocardiogram, ventricular developed pressure (VDP), and heart beating rate, were studied. Cadmium (10 to 100 muM) significantly decreased VDP of the isolated shark hearts in a reversible manner. However, heart beating rate was not affected by cadmium. Cadmium also induced a transient modification of the amplitude and the form of the QRS complex. Cupric ion transiently increased VDP in a concentration-dependent manner, whereas cuprous ion (1 to 100 muM) did not markedly alter the cardiac functions of shark. Cupric or cuprous ions did not change heart beating rate and electrocardiogram at concentrations of 10 to 100 muM. Our results, for the first time, demonstrated the effects of cadmium on shark heart and indicated that the cardiac effects of copper are valence dependent. An elucidation of heavy metal effects on fish cardiac functions will help to understand the complex toxicological properties of heavy metals in different species and tissues, and will provide information for management of pollution control and marine resource protection.